[Determination of platelet serotonin in obsessive-compulsive disorders].
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Biomedical subjects
Publications and source records attributed to B Renaud.
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The present study describes the first experimental evidence for a direct projection of the medulla oblongata adrenergic (Ad) neurons to the rat pontine structures by using the indirect immunoperoxidase technique. Three weeks after unilateral electrolytic lesion of the longitudinal axon bundle in the medulla oblongata, the morphological changes of the phenylethanolamine-N-methyltransferase (PNMT)-immunoreactive (IR) structures located in the rat brainstem have been analysed. In the lesioned rats we observed a decrease in the number of PNMT-IR structures in virtually all regions of the brainstem ipsilateral to the lesion, especially in the locus coeruleus (LC). These results indicate that the PNMT-IR terminal-like fibers of the LC are derived from the ipsilateral medulla oblongata Ad neurons and are mainly provided by the longitudinal axon bundle.
Separate populations of serotonin- and adrenaline-containing neurons exist in the ventrolateral medulla oblongata and project to the intermediolateral cell column of the spinal cord. The medullary serotonin nuclei appear to constitute a heterogeneous group with diverse effects on arterial pressure. Microinjections of sodium glutamate (which excites cell bodies but not axons of passage) made in the area of the ventrolateral serotonin cells evokes an increase in arterial pressure which is abolished by prior 5,7-dihydroxytryptamine (5,7-DHT) treatment. In contrast, glutamate microinjection in the area of the serotonin-containing cell bodies in the midline of the medulla evokes falls in arterial pressure and these responses are attenuated by pretreatment with 5,7-DHT. Glutamate microinjection made in the ventrolateral medulla in the area of the adrenaline-containing cells, evokes increases in arterial pressure which are not altered by 5,7-DHT pretreatment. After ablation of the area of the adrenaline-containing cells by electrolytic lesion, the pressor function of the ventrolateral serotonin-containing cells is still observed. These results suggest that although the serotonin-containing neurons of the ventrolateral medulla are closely aligned with the ventrolateral adrenaline area, the serotonin cell groups and the cells of the adrenaline area exert their pressor actions independently.
In this study, we sought to determine if there was an interaction between the C2 adrenaline-containing (A) neurons of the rat medulla oblongata and the noradrenaline-containing (NA) cell bodies of the locus coeruleus (LC). For this purpose, the biochemical response of the NA cell bodies of the LC after a lesion of the C2 region was studied by using as markers the in vitro activities of the catecholamine synthesizing enzymes: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT). An increase in TH activity, not associated with any change in DBH or PNMT activity, was found in the LC (+104%, P less than 0.001) 4 days after a bilateral electrolytic lesion (3 mA for 5 s) of the C2 region. Conversely, the electrolytic lesioning of the neighboring A2 region of NA neurons did not modify the TH activity of the LC. These results suggest the existence of an ascending adrenergic inhibitory control of the NA cell bodies of the LC.
The responses of the noradrenaline (NA)- and adrenaline (A)-containing neurons to a reserpine treatment have been studied in the rat brain by using biochemical indices of the neuronal activity. Three days after multiple reserpine injections, tyrosine hydroxylase activity was significantly increased in the locus coeruleus (LC), A1-C1 and C2 regions. No change in this activity was observed in the A2 region. Furthermore, the NA and A endogenous levels were markedly reduced both in NA and A cell bodies and/or terminals, suggesting a reserpine action on NA and A neurons. The NA turnover was unchanged in all the regions analyzed. Conversely, the A turnover was reduced in the LC, A2 and C2 regions and in the nucleus periventricularis of the hypothalamus. This result suggests a different degree of sensitivity and/or response of the NA and A neurons following reserpine administration.
In brain regions containing noradrenergic (NA) cell bodies or terminals, DSP-4 induces changes in the activity of catecholamine-synthesizing enzymes which suggest that central NA neurons are lesioned by this neurotoxin. In contrast, the lack of change in the same enzymatic activities in an area containing mostly adrenergic (A) neurons (C2 region), favors the hypothesis of a resistance of the A neurons to DSP-4. Furthermore, the enzymatic changes observed in peripheral organs suggest a peripheral activation of the NA cell bodies in response to lesioning of the sympathetic terminals by DSP-4.
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We have studied the effects of withdrawal from chronic clonidine treatment in the adult male spontaneously hypertensive rat (SHR). SHR received clonidine, 0.1 mg X kg-1 X day-1 i.v. for 10 days. Clonidine was delivered via osmotic minipumps. After 7 days of treatment there was a 16.5 +/- 2.5 mm Hg fall in mean arterial pressure. This was accompanied by a decrease in the dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase activities of the A1/C1 region. Withdrawal from clonidine was characterized by tachycardia and an increase in mean arterial pressure and heart rate lability. Phenylethanolamine-N-methyl transferase of the the dopamine-beta-hydroxylase activity remained diminished. The dopamine-beta-hydroxylase activity of the A2/C2 region was also diminished during withdrawal. We suggest that the blood pressure lowering effect of clonidine is accompanied by a decreased capacity to synthesize adrenaline in the A1/C1 region where adrenaline could mediate a pressor effect. Increased blood pressure lability during withdrawal is accompanied by a restoration of synthesis of adrenaline in the A1/C1 region. There is also a decrease in the capacity of synthesis of noradrenaline in the A2/C2 region where adrenaline may mediate a vasodepressor effect.
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The concentration of the three major catecholamines (CAs) were determined in 500 micron thick coronal sections of the rat medulla oblongata dissected into microcubes. Noradrenaline (NA) concentrations were always found much higher than the levels of the two other CAs in the same microcube. The highest concentrations of the three CAs were found in the dorso-medial region of the lower brainstem, more exactly in the more caudally located parts of the nucleus tractus solitarii (NTS). In the ventro-lateral region, the CA concentrations were lower and, except for adrenaline (A), did not exhibit any substantial change in their rostro-caudal distribution. Conversely, in the dorso-medial region, there was a clear rostro-caudal pattern of distribution of the three CAs. This distribution was similar for the three amines, since only a small difference (about 500 micron) was found between the maximal NA and A concentrations. Since the three CAs are present in highest concentrations within the same dorso-medial or ventro-lateral groups of microcubes, a microdissection of these two areas seems suitable to study simultaneously the metabolism of the three CAs in the rat lower brainstem. These data also suggest a microdissection procedure to study A metabolism within the C2-C3 A cell bodies and within a region more caudally located, rich in A terminals.
The rate of tryptophan hydroxylation in vivo is unaltered in brain areas of 5, 9 and 21 week-old Lyon genetically Hypertensive (LH) rats as compared to both Lyon Normotensive (LN) and Low Blood Pressure (LL) rats, except for a decrease in the C1 area of the medulla oblongata in 9 week-old animals.
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By using a new microdissection procedure allowing the noradrenaline (NA) and adrenaline (A) cell groups of the A2-C2 region to be sampled preferentially, it was possible to study the biochemical response of these two neuronal populations after 6-hydroxydopamine (6-OHDA) administration. Five days after an intraventricular 6-OHDA injection, tyrosine hydroxylase (TH) activity increased (+104%, P less than 0.01) in the adrenergic C2 region, in the locus coeruleus (LC) and in the A1-C1 region, while the NA A2 region exhibited no significant increase. Twenty-one days after 6-OHDA administration, dopamine-beta-hydroxylase (DBH) activity had decreased in both the noradrenergic regions (LC, A1-C1 and A2 regions) and in the C2 adrenergic region. Conversely, phenylethanolamine-N-methyltransferase (PNMT) activity was not modified either in the cell bodies or in the terminals located in the tractus intermediolateralis of the spinal cord and in the hypothalamic nuclei. These data suggest: (i) that adrenaline-containing neurons could be sensitive to the neurotoxic action of 6-OHDA since they exhibit changes in TH and DBH activities; and (ii) that the determination of PNMT activity may not be sensitive enough to estimate the functional integrity of the A cell bodies or terminals.
Homovanillic acid and 5-hydroxyindoleacetic acid, respectively the major metabolites of the central neurotransmitters dopamine and serotonin, are present in human lumbar cerebrospinal fluid, and their determination during the probenecid test is used to study brain monoamine abnormalities in man. We developed a high performance liquid chromatographic technique coupled with electrochemical detection which allows the simultaneous determination of homovanillic acid and 5-hydroxyindoleacetic acid on 10 microliter of human lumbar cerebrospinal fluid. Another liquid chromatographic technique coupled with ultra-violet detection was applied to the measurement of probenecid after injection of 10 microliter of native cerebrospinal fluid. The main advantages of these two techniques are their simplicity, sensitivity, rapidity (five cerebrospinal fluid samples are analysed within one hour) and their good day-to-day reproducibility . These methods were applied to probenecid tests performed in several neurological patients.
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The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-beta-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (+49.0%, P less than 0.001 and +36.6%, P less than 0.001, respectively) and DBH activity was also increased in the superior cervical ganglia (+22.8%, P less than 0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.
Since there was no study available on the comparative anatomical neurochemistry of the noradrenaline (NA) and adrenaline (A) containing neurons of the lower brain stem, we studied the distribution of the activities of the three major catecholamines (CA)-synthesizing enzymes in coronal sections of the rat medulla oblongata dissected into microcubes. In the dorso-medial region, there was a 1500 micron rostro-caudal difference in the localization of the peak of PNMT activity compared with the peaks of TH and DBH activities. This result led to a new microdissection technique allowing the preferential microdissection of the C2 A neurons versus the A2 NA neurons. The response of these two populations of CA neurons was then studied after a sustained decrease in blood pressure induced in young SHR by a 14 days dihydralazine treatment. The C2 adrenergic region exhibited an overall increase in TH, DBH and PNMT activity (+69%, +45% and +33%; p less than 0.01 respectively) while the A2 noradrenergic region was unaffected. Thus, the NA and A neurons of the rat dorso-medial lower brain stem do not seem to exhibit the same biochemical response after a prolonged hypotension. This preliminary result favors the hypothesis of a different functional role for the neighboring A2 and C2 neurons in central control of blood pressure.
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